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Rom J Leg Med [23] 193-202 [2015]
DOI: 10.4323/rjlm.2015.193
© 2015 Romanian Society of Legal Medicine Genetic basis of aggression: Overview and implications for legal proceedings
Smilja Teodorović1,*, Bogdan Uzelac1
_________________________________________________________________________________________
Abstract: History and patterns of aggressive behavior represent an integral part of the offender’s profile during forensic
investigations. Traditionally, the majority of evidence on determinants of criminal behavior is contributed by environmental
data. In the past two decades, a growing body of research in the fields of neurobiology and genetics has immensely enriched
our understanding of the topic. This paper provides a systematic overview of genetic factors believed to govern the development
of aggressive and criminal behavior in humans. A particular emphasis is given to the polymorphisms of genes involved in
serotonergic and dopaminergic metabolisms in relationship to varying aggressive behavioral outcomes. In addition to approaches
focused on individual genes, whole genome analyses, interplay between genetic factors, as well as gene-environment interactions,
are also discussed with respect to this complex behavior. Finally, severity of incorporating these findings into the justice system,
as well as the importance of considering them in contemporary criminalistics, are contemplated.
Key Words: aggression, violence, genetics, behavioral, genes, monoamine oxidase A.
A
ggressive behavior, characterized by
a conscious tendency to harm others
against their will, can be exhibited through illegal,
violent and antisocial behavior and is often present in
criminal offenses. It is a complex behavior, regulated
by multiple factors, including environmental, cognitive,
neurobiological and genetic [1]. Twin and adoption
studies played a significant role in behavioral genetics
[2]. For instance, Rushton et al. assessed heritability and
individual differences regarding five traits (aggression,
altruism, empathy, assertiveness and nurturance)
on 573 pairs of adult twins, suggesting that a genetic
component is crucial in the development of aggression
[3]. The progress in cytogenetics and molecular biology
in the second part of the 20th century allowed examining
relationships between genetic factors and aggressive and
criminal behaviour, first at the chromosomal level and
later at the level of single nucleotides. The intent of this
review is to present key findings in the field and point out
their applicability in the legal system.
Chromosomal aneuploidies
Jacob’s syndrome (XYY) affects one in 1000
males, most of which are educated normally and lead
healthy lives, despite lower IQ. Given that society
traditionally tends to view aggression as a male
behavioral pattern, in the 1960s Patricia Jacobs and
colleagues hypothesized that “supermales” with an extra
Y chromosome will be overrepresented in a population
of 197 psychiatric institution inmates, previously
qualified as „mentally retarded” with dangerous, violent
or criminal tendencies [4, 5]. The results revealed XYY
incidence of 3.5% in examined population, compared
to 0%-0.2% in the general population [6]. However, this
study failed to take into account reasons for being in a
mental institution (mental illness vs. aggression), history
1) Academy of Criminalistic and Police Studies, Forensics Department, Belgrade, Serbia
* Corresponding author: Assistant Professor, Academy of Criminalistic and Police Studies, Forensics
Department, Cara Dušana 196, 11080 Belgrade, Serbia, Tel.: +381-11-3107-172, Fax:+381-11-3162-150,
Email: [email protected]
193
Teodorović S. and Uzelac B.
Genetic basis of aggression: Overview and implications for legal proceedings
of abnormal behavior, type of criminal acts that the
subjects are prone to, etc. Other studies confirmed the
overrepresentation of XYY genotype in penal or mental
institutions, but also suffered from sampling bias, due
to preselecting affected males [7, 8]. By screening 34380
infants, Gotz and colleagues assessed 16 XYY males
for antisocial personality disorder (APD) and 17 XYY
males for criminal conviction frequencies and suggested
that these measures were higher in affected males
compared to healthy controls due to lower intelligence
[9]. Additional longitudinal studies examining affected
males from general population revealed that XYY men
are not at greater risk of being incarcerated compared to
healthy men, as early works suggested [10, 11]. In fact,
several lines of evidence point out that the most common
criminal acts among XYY males are proprietary offenses,
thus not characterized by more violence [9, 12]. A recent
Table 1. Key candidate genes discussed as risk factors for
aggressive behavior
Gene
name
Risk polymorphism/allele
MAOA
C936T (exon 8)
30bp VNTR (promoter)
CAn (intron 2)
5-HTT
TPH1
TPH2
SNP identification
number
rs72554632
44bp insertion/deletion
(promoter)
17bp VNTR (intron 2)
А218C (intron 7)
A779C (intron 7)
haplotype (intron 5-8)
A (upstream)
rs1800532
rs1799913
C_8872342
C_15836061
rs7305115
C_8872308
rs1352251
rs1473473
rs6582071
5-HT-2A C (promoter)
rs6311
COMT
Val158Met
rs4680
DRD2
TaqIA RFLP (downstream)
DRD4
C
DAT1
40bp VNTR (3’ UTR)
BDNF
C
T
rs7103411
rs10767664
HTR1E
A
rs1406946
PNMT
T
rs2934966
*rs – reference SNP
194
rs3758653
longitudinal study from Denmark compared conviction
rates for eight crime types between 161 XYY men and
15356 controls, ages 15-70 [13]. Results indicated a
significant increase in violent criminal offenses (sexual
abuse, homicide, burglary, violence and arson) in XYY
men. However, when socioeconomic variables such as
poverty, social exclusion and inadequate upbringing,
as well as intellectual functioning were also taken into
account, criminal patterns decreased to levels comparable
to controls.
Klinefelter syndrome (KS) (XXY) is present
in 1/581 to 1/917 individuals and is characterized by
a specific phenotype [14]. In 1988, Miller proposed
higher frequency of arson by KS individuals compared
to general public [15]. Gotz et al. failed to confirm
association between KS men and APD incidence, as well
as criminal conviction rate, although small sample size
must be noted [9]. The abovementioned Danish study
also compared conviction rates between 934 KS men
and 88979 healthy controls and reported an increase
in sexual abuse, burglary and arson in KS individuals,
although this could also be due to possible testosterone
therapy [13]. Again, socioeconomic parameters reduced
the observed risk to levels seen in controls.
Other chromosomal aneuploidies have also been
considered in terms of violent behavior. For instance, 48,
XXYY men were indicated to be more likely to exhibit
aggressive and delinquent behavior in comparison to 48,
XXXY and 49, XXXXY individuals [14]. Yet, it is clear
that these rare chromosomal disorders could not account
for the widespread violence, shifting the focus to putative
candidate genes.
Candidate genes
Neurotransmitters monoamines (serotonin,
dopamine, adrenaline, noradrenaline, histamine) can
affect mood and behavior, as well as awakeness, memory
and sexual drive [16] and several lines of evidence
suggested that serotonin deficiency is connected
to impulsivity, violence and aggression [17]. Thus,
numerous candidate genes have been researched in
association with aggressive traits (Table 1), including
genes involved in serotonin metabolism (5-HTT, TPH),
dopamine metabolism (DRD2, DRD4, DAT1) and
enzymatic degradation (MAOA, COMT).
The infamous MAOA gene
Monoamino oxidase A (МАОА) is a
mitochondrial enzyme involved in deamination of excess
monoamines. As impulsivity, mood swings, aggression,
sleep disorders, depression and sexually deviant behavior
have been noted in MAOA deficient individuals, MAOA
gene variants have been hypothesized in development of
violent criminal behavioral patterns [18]. Brunner et al.
(1993) examined males in a large Dutch family with a
history of borderline mental retardation and abnormal
Romanian Journal of Legal Medicine behavior (impulsive aggression, rape attempts, arson, and
exhibitionism) [18]. Five subjects exhibiting the behavior
possessed MAOA deficiency in vitro, due to a missense
C936T mutation in exon 8. Although the genetic basis
for the inability to control impulsive anger has been
proposed, this rare single nucleotide polymorphism
(SNP) has not been reported since. Yet, rodent studies
report higher aggression rates, as well as maladaptive
defensive reactivity and enduring responses, in MAOA
deficient mice [19, 20].
Six variants (2, 3, 3.5, 4, 5 and 6 repeats (R)) of a
30bp MAOA upstream variable number tandem repeat
(uVNTR) have been described in the promoter region[21,
22]. It has been suggested that 3.5R and 4R are optimal
transcription activator elements, given that they result
in significantly higher MAOA expression (MAOA-H) in
vitro, compared to 3R and 5R (MAOA-L) [22], although
contrasting findings have been reported for 5R [23]. In an
attempt to link MAOA alleles with aggressive behavior,
Manuck and colleagues genotyped 110 Caucasian males,
suggesting that 3R and 5R carriers score significantly
lower on aggressiveness and impulsivity, but not lifetime
aggression or hostility, in comparison to 3.5R and 4R
men [24]. Others indicated the protective/low risk nature
of 4R allele [25], which persist across cultural settings,
as 3R variant was associated with impulsive/antisocial
behavior in 125 Brazilian alcoholics of European origin
[26].
Beaver and colleagues examined 2196 individuals
from the National Longitudinal Study of Adolescent
Health and found that 2R and 3R male carriers are 1.94
times more likely to belong to a gang and 1.82 times more
likely to use weapons for fighting, compared to 3.5R, 4R
and 5R carriers [27]. In addition, 2R and 3R allele gang
members were 4.37 times more likely to use weapons
in comparison to gang members with other genotypes,
which may explain the variability in levels of violence
among gang members. A recent study on 49 violent
and 40 nonviolent male prisoners showed that 2R and
3R alleles are significantly more present in incarcerated
Caucasians who performed violent, as opposed to
nonviolent crimes [28]. Importantly, this association was
only marginally true for African American population,
although it is unclear whether this is due to racial
differences or sampling.
In an attempt to elucidate individual contribution
by 2R and 3R alleles to aggressive traits, Guo and
colleagues analyzed 2524 participants from the same
dataset and reported that 2R carriers report at least twice
as much delinquency in adolescence, young adulthood
and adulthood compared to men with other alleles
[29]. Increased violence, arrest and incarceration rate
during lifetime [30], as well as increased risk of stabbing
and shooting multiple victims during adolescence and
childhood [31] have been reported for 2R carriers, as
opposed to other genotypes, in African American males.
Vol. XXIII, No 3(2015)
A comprehensive meta-analysis considering
31 independent studies on MAOA-uVNTR examined
low activity/high risk (2R, 3R) and high activity/low
risk (3.5R, 4R) genotypes, while data for 5R allele was
treated as per original research [32]. The results show
only a modest positive association between low activity
alleles and antisocial behavior, the heterogeneity from
different studies attributed to context-dependent role of
low activity genotypes on antisocial behavior.
Another MAOA polymorphism of a dinucleotide,
CA, repeat in intron 2 (MAOA-CAn), has also previously
been described [33]. After eight MAOA-CAn alleles
have been dichotomized into short (< 114bp) and long
(>114bp), Vanyukov and colleagues reported a lack of
association between the repeat length and measures
of aggressiveness or conduct disorder in adolescents
[34]. Manuck et al. observed slightly lower aggression/
impulsivity scores in men with long MAOA-CAn alleles,
although this difference only approached statistical
significance [24]. Interestingly, these results have been
reported despite the linkage disequilibrium between
MAOA-CAn and MAOA-uVNTR.
Finally, given that MAOA is X-linked, genetic
variance in aggressive behavior has typically been
pursued for males and not females.
Despite many associative findings, a study based
on an in vivo imagining of MAOA concentration alone,
disputed the association with uVNTR [35]. Similarly,
Widom and Brzstowitz emphasized that MAOA genotype
alone typically does not play a role in forming aggression
in individuals [36]. Such results must also be considered,
together with the fact that not all individuals with
“risky” alleles/genotypes (if documented) will exhibit
aggressiveness. Additionally, it is well documented in
the literature that adverse environmental factors, such
as childhood abuse, increase the chance of developing
antisocial personalities or performing violent criminal
offenses [37]. Taken together, these arguments emphasize
the significance of accounting for adverse environmental
conditions and genetics (GxE) when studying the basis of
aggressive behavioral patterns.
Caspi and colleagues typed 540 Caucasian
males from the New Zealand Dunedin Multidisciplinary
Health and Developmental Study and assessed four
antisocial behavior criteria (deviant behavior, conviction
for a violent criminal offence, predisposition to violence
and antisocial personality symptoms), reporting that
12% of examinees have low MAOA genotype/activity
(3R and 5R) together with an abusive childhood and that
44% of all men sentenced for violent crimes belong to
this category [38]. High MAOA genotype/activity males
(3.5R and 4R), on the other hand, appear to be able to
moderate their behavior, despite the childhood abuse
[21, 39]. Many researchers have argued that MAOA
genotype will predispose to aggression only in the
particular environmental context, such as early traumatic
195
Teodorović S. and Uzelac B.
Genetic basis of aggression: Overview and implications for legal proceedings
experiences, maltreatment, strict parenting style, etc. [21,
25, 26, 36, 37, 39-44], although conflicting reports exist
[45]. Thus, a specific GxE model of behavioral outcome
has emerged from the presented research, which
appears to be restricted to male Caucasians, either due
to varying childhood environmental factors or varying
impact of MAOA-regulated polymorphisms on MAOA
metabolism between races [46]. Importantly, McDermott
and colleagues conducted a controlled experiment in
which they observed a higher incidence of demonstration
of aggressive behavior in low, compared to high, MAOA
genotype/activity males, as response to financial loss [47].
These results were more pronounced when the extent of
provocation was higher.
5-HTT Gene
Serotonin transporter recycles serotonin in the
synaptic space, hence serotonin transporter gene (5HTT) has been implicated in behavioral research. A
5-HTT gene–linked polymorphic region (5-HTTLPR)
in the transcriptional control region of the gene exists in
long (La), 528bp, and short (S), 484bp, forms due to a 44bp
insertion/deletion [48]. As opposed to SS homozygotes
and heterozygotes, LaLa homozygotes (~32% frequency)
exhibit high transcriptional activity in vitro and two fold
higher serotonin uptake [39, 48-50].
Beitchman and colleagues found that the
incidence of genotypes contributing to low expression
levels is significantly higher in a group of 82 healthy
girls and boys, who have shown aggressive behavior
for at least 2 years [51]. Retz et al. detected significant
overrepresentation of SS genotype in Caucasian violent
offenders, when analyzed 132 criminal and 21 civil
offenders [52] and similar results have been reported for
Chinese males [53]. Yet, as it has been proposed that only
5% of violent behavior can be attributed to the 5-HTTLPR
[52], researchers have also analyzed behavioral
outcomes of low expression genotypes in the presence
of environmental stressors. In an analysis of 847 young
Caucasians from Dunedin Multidisciplinary Health
and Development Study, Caspi and colleagues reported
greater suicidal tendencies (autoagression) (14%) in
S allele carriers, when faced with repeated stressful life
situations [39]. Conway and colleagues genotyped 381
mostly Caucasians, but also Asian Pacific Islanders and
Aboriginals, and suggested that 5-HTTLPR genotype may
contribute to aggressive response to chronic, rather than
acute stress [54]. Others have corroborated these findings
[42, 55]. To test for GxE, Cicchetti et al. investigated 627
children, using self-, peer- and adult behavioral reports
of maltreated, low income subjects [56]. Maltreated
children with LaLa genotype exhibited decreased risk
for development of delinquent behavior, regardless of the
abuse onset and timeframe. These results were confined
to maltreated children, indicating that genotype alone
does not predict antisocial behavior.
196
A meta-analysis which included 18 studies
reported that there exists only a moderate positive
association between 5-HTTLPR S allele and ASB and
that studies which are based on small sample sizes tend to
overrepresent the role of 5-HTTLPR [32]. On the other
hand, some studies, while based on modest number
of subjects, bring value in terms of the experimental
approach. For instance, Beitchman and colleagues
specifically typed for a third, rare allele, Lg, which
results from a substitution of a single base in La leading
to low transcription, suggesting that previous grouping
of Lg with La could have contributed to curbing the S/
La differences [51]. On the other hand, Ni et al. did not
find an association between 5-HTTLPR and borderline
personality disorder (BPD), even when considering Lg
and S alleles together [57].
Another 17bp VNTR in 5-HTT gene intron 2
has been described and implicated in transcriptional
regulation, such that 12R form acts as a significantly
stronger transcriptional enhancer compared to 10R allele
[58]. Analyzing subjects from familial schizophrenia,
approximately 30% lower 5-HTT mRNA levels were
observed in “low expressing” genotypes (10/10 and
10/12), compared to a “high expressing” (12/12),
although the difference was not statistically significant.
Higher frequency of a 10R allele and a lower frequency
of a 12R allele, in comparison to controls, have been
linked with BPD [57] and autoagression [59], although
this individual effect is likely weak. Rather than making
conclusions from allelic differences, when Hranilovic and
colleagues analyzed haplotypes (high expressing at both
loci, low expressing at only one locus and low expressing
at both loci), potential combined effect of the two regions
on 5-HTT gene expression was observed [50]. Ni and
colleagues also argue in favor of the combined effect in
increasing serotonin concentration in the synaptic cleft
[57].
TPH1 and TPH2 Genes
Concentration of 5 hydroxy indol acetic acid (5HIAA), one of the products of serotonin degradation by
tryptophan hydroxylase 1 (TPH1), is considered a reliable
indicator of serotonin turnover in the brain [18]. Manuck
et al. genotyped 251 males and females and proposed
that the presence of TPH1 SNP А218C corresponds
to higher aggression levels, as well as perception and
manifestation of unprovoked rage [24]. Another study
addressed an A779C transversion which contributes to
an “upper” (U) and “lower” (L) allele, and is in strong
linkage disequilibrium with А218C, in 154 healthy
subjects and 86 suicide attempters of German origin
[60]. Differences in allele/genotype frequencies were not
reported in two examined groups. Yet, U allele carriers
were associated with higher state and trait anger, as well
as angry temperament, indicating the contribution of
TPH1 gene in manifestation of aggression. A recent meta-
Romanian Journal of Legal Medicine analysis based on 37 studies and both polymorphisms of
interest yielded a positive significant association with
autoaggressive behavior [61]. Yet, there also exist studies
which observed a lack of this association [62, 63]. It should
be noted that when Cicchetti and colleagues typed two
SNPs in maltreated children, rs18000532 and rs1799913
resulting in G and T alleles, genotype alone did not show
association with antisocial behavior [56]. Yet, when GxE
interaction was considered, T allele carriers who have
been maltreated were more likely to exhibit delinquent
behavior, particularly if they fit the early onset/recent
maltreatment profile.
A rate limiting enzyme in serotonin synthesis in
the brain is triptophan hydrolase 2 (TPH2). Zhou and
colleagues genotyped 1798 individuals from 4 populations
(African American, US Caucasians, Finish Caucasians
and American Indians), who were either healthy or
characterized by previous suicide attempts, major
depression and/or anxiety disorder [64]. The researchers
identified a “protective” and a “risk” haplotype between
TPH2 introns 5 and 8 (~52kb) for anxiety, depression
and autoaggression in examined Caucasians and African
Americans. This concurs with results seen by others,
including association with BPD, cognitive impulsiveness
in ADHD patients and aggression affect lability [65-67].
Conflicting findings have also been reported [61, 68],
although direct comparisons are challenging, given that
some studies utilized distinct set of markers.
Other candidate genes
A study on 203 suicide attempters and 363
healthy German subjects indicated that the C allele of the
functional SNP rs6311 in the promoter of the serotonin
receptor 2A (5-HT-2A) gene is associated with aggressiverelated behavior and less inhibition of aggression, while a
CC genotype correlates to increased anger and aggressiverelated behavioral patterns [69]. A more comprehensive
study assessed 582 SNPs in 14 genes related to serotonin
function in 1180 children from the International
Multicenter ADHD Genetics study, implicating role
of both serotonergic and dopaminergic systems in
aggressive impulsivity [65]. However, none of the
analyzed polymorphisms showed prominent association
with impulsive aggression, while only a single SNP in
phenylethanolamine N-methyltransferase (PNMT)
gene exhibited gene-wide statistical significance for
cognitive impulsivity. Six SNPs from five genes previously
associated with ADHD show nominal significance
for influencing impulsive aggression: rs7103411(C)
(BDNF), rs10767664(T) (BDNF), rs3758653 (DRD4),
rs1406946(A) (HTR1E), rs2934966(T) (PNMT) and
rs6582071(A) (TPH2). Oreland and colleagues also
report main effect of BDNF genotype on adolescent
criminality in the presence of family maltreatment [42].
A functional polymorphism in the catecholO-methyltransferase (COMT) gene, G/A in codon 158
Vol. XXIII, No 3(2015)
resulting in Val (“high activity” H allele) to Met (“low
activity” L allele) substitution, leads to 3-4 times greater
COMT activity in HH compared to LL individuals, while
HL subjects have an intermediate phenotype [70]. One
study which investigated anger-related characteristics
in 149 suicide attempters and 328 healthy subjects from
Germany found higher L allele/genotype frequencies
in violent compared to other suicide attempters and
suggested that LL genotype confers overt aggression, HH
genotype inward aggression, while heterozygotes appear
to have protective advantage [71].
A functional TaqIA RFLP in dopamine
receptor D2 (DRD2) gene, resulting in A1/A2 alleles,
has been implicated in impulsive, violent and criminal
behaviors [72-77]. Guo and colleagues argued that A1A2
heterozygotes are more prone to serious and violent
delinquency, compared to either of the homozygotes
[75]. Others have shown that A2A2 DRD2 genotype
is overrepresented in subjects who do not get involved
in criminal behavior [78]. Analyzing 40bp VNTR of
dopamine active transporter 1 (DAT1) gene, resulting in
9R and 10R alleles, in over 2500 adolescents and young
adults, Guo et al. published that 10R carriers are twice
as likely to get involved in serious and violent delinquent
behavior [75].
Nitrogen oxide synthetase (nNOS) gene
is involved in metabolism of nitrogen oxide (NO),
neurotransmitter found in parts of the brain involved in
emotional regulation [8]. nNOS knockout mice (nNOS/-) exhibit notable NO deficiency in the brain and an
increase in aggressive and inappropriate sexual behavior
[79, 80], particularly in the context of social exclusion
(“single-housed males”). The authors also illustrated
NO and serotonin interaction in the brain, thus
nNOS disorders could significantly impact serotonin
metabolism.
Yet, a recent comprehensive meta-analysis,
which synthesized 185 studies on 12 polymorphisms
and ~60000 subjects, argues lack of association between
analyzed candidate genes and violent and aggressive
outcome [81]. These findings concur with an idea that
complex behaviors are likely governed by hundreds of
thousands of genes and point out that a quest for genetic
determinants of aggression/violence requires different
approaches.
Gene-gene interactions
Ten serotonergic genes were tested in BPD
patients and significant interactions between 5-HT2C
and TPH2, as well as among 5-HT2C, 5-HTT, MAOA
and TPH2 have been reported (Table 2) [63]. Another
study investigated the role of GxGxE in development
of criminality in 1819 Swedish adolescents [42]. 5-HTT
gene showed interaction with MAOA and BDNF genes,
with or without family maltreatment, while MAOA and
BDNF genes revealed interaction only in the presence of
197
Teodorović S. and Uzelac B.
Genetic basis of aggression: Overview and implications for legal proceedings
Table 2. Gene-gene interactions proposed to predispose to aggressive behavior
Genes/Adverse environment
5-HT2C/TPH2
5-HT2C/MAOA/TPH2
5-HT2C/5-HTT/MAOA/TPH2
5-HTT/MAOA
5-HTT/MAOA/family maltreatment
5-HTT/BDNF
5-HTT/BDNF/family maltreatment
MAOA/BDNF/family maltreatment or sexual abuse
MAOA/BDNF/5-HTT/family maltreatment or sexual abuse
DRD2/DRD4
Risk polymorphisms
rs6318/rs2171363
rs6318/VNTR/rs2171363
rs6318/VNTR/VNTR/rs2171363
na
na
na
na
na
na
TaqIA RFLP/48bp VNTR
References
[63]
[63]
[63]
[45]
[45]
[45]
[45]
[45]
[45]
[81-82]
*na – not available
family maltreatment or sexual abuse.
Additionally, the interaction between all three
genes and family maltreatment or sexual abuse was
found, with the most extreme haplotypes (MAOA LL,
5-HTT LL, BDNF Val-Val and MAOA SS/LS, 5-HTT
SS/LS, BDNF Val-Met/Met-Met) scoring the highest for
criminality (Table 2).
Researchers also addressed the interaction
between DRD2 and DRD4 (48bp VNTR which can be
repeated between 2 and 11 times) on the development
of criminal behavior in 1725 young Americans and
found association with major theft and burglary, gang
fighting, but not physical assaults [82, 83]. DRD2 A1
and DRD4 alleles with 7R repeats or more are proposed
as risk conferring and each of the two alleles appears to
strengthen the effect of the other gene (Table 2). Similarly,
Oades and colleagues considered joint gene influences
and found that DRD4 C allele was overexpressed and
HTR1E and TPH2 A alleles underexpressed in overt
impulsivity [65].
Whole genome analyses
When whole genome analysis of 3963 individuals
was performed, four polymorphisms displayed significant
genome-wide association with childhood conduct
disorder, two in intergenic regions on chromosomes 11
and 13, and two in C1q and tumor necrosis factor-related
protein 7 (C1QTNF7) gene, but none in traditional
candidate genes [84]. Tielbeck and colleagues focused on
1649 adults and found the strongest, albeit not significant
genome-wide, association between antisocial behavior
and chromosomes 5, 14, 15 and 21 [85]. Similarly, no
SNPs or genes were identified to associate positively on a
genome-wide scale. A gene for dual specificity tyrosinephosphorylation-regulated kinase 1A (DYRK1A), one of
the candidate genes for mental retardation, and its three
SNPs (rs12106331, rs2835702 and rs2835771) showed
the most association. Specific search for a link between
antisocial behavior and previously reported candidate
genes, including MAOA, did not yield any findings. A
study on behavioral disinhibition (including risky and
198
impulsive behavior) in 1901 adolescents reported lack of
individual locus or SNP association with genome-wide
significance [86]. Yet, seven new loci (MAGI2, NAV2,
CACNA1C, PCDH9, MYO16, IQCH and DLGAP1)
emerged in gene-based association tests.
It must be noted that although genome-wide
association of individual genes/SNPs has not been
detected, genetic contribution of behavioral variance is
typically around or above 50% [85, 86]. Therefore, further
whole genome analyses involving drastically larger sample
size and the effects of adverse environmental factors will
be of great benefit.
Consideration of genetic basis of aggressive
behavior in criminal trials
Only 81 court cases in which genetic makeup impacted the imposed sentence for violent crimes
occurred worldwide from 1994-2011 [87]. In several
court cases in the US, such as People v. Tanner [88],
defense attorneys attempted to prove lack of rational
and moral judgment at the time of the crime due to XYY
genotype [89]. In the case of Stephen Mobley, accused of
murdering a restaurant manager during a robbery in 1991,
defense appealed a death sentence requesting Mobley be
tested for a MAOA mutation [90]. The court rejected
the appeal, stating insufficient scientific validation. Two
decades later, on the contrary, Davis Bradley Waldroup’s
jail sentence was reduced from 1st degree murder to
voluntary manslaughter, due to a MAOA deficiency in
the brain [91, 92]. In 2007, Abdelmalek Bayout was on
trial in Italy for stabbing to death Walter Felipe Perez,
who allegedly provoked him on religious basis [93]. After
Bayout was found to have “risky” forms of five genes
(including MAOA) previously implicated in aggressive
behavior in stressful situations, the judge shortened the
jail sentence. Similarly, Stefania Albertani’s sentence for
murdering her sister in 2009 was reduced from life in
prison to 20 years, due to low MAOA activity and changes
in gray matter of frontal cingulate gyrus (involved in
controlling behavioral inhibitions) and insula (which has
been linked to aggression) [93].
Romanian Journal of Legal Medicine Previous examples illustrate a more liberal
approach employed by Italian courts. Yet, as seen from
genome-wide and interaction studies, single gene
investigations can be quite misleading and expensive for
the judicial system, given that complexity of elucidating
determinants of aggressive behavior lies in the number
of involved variables and their interplay (Genetic x
Environmental x Neurobiological x Cognitive). In order
to gain better scientific validation, it will be essential
to increase the number of longitudinal studies and
number of subjects, consider the function of hundreds
of thousands of genes/the entire genome, possible
protective effects of other genes, sustainability of results
in all ethnical groups, differentiate between types of
violence, impulsive vs. premeditated aggression, employ
more objective criteria for evaluating aggression, rather
than self-assessments, etc. Therefore, despite impressive
progress in the field in the past two decades, it is essential
that courts exercise extreme caution when considering
the idea of amending criminal responsibility on the basis
of genetic predisposition, such as to avoid overestimating
the power of the results still premature for use in the legal
system, due to lack of causation.
Vol. XXIII, No 3(2015)
CONCLUSION
While genetics has gained increasing importance
in criminalistics and forensics, the public stands divided
between providing legal protection for individuals
suffering from genetic abnormalities and preventing
these aggressive individuals to repeatedly harm others.
Even though the research in the field has not given a
“one fits all” solution, data coming from whole genome
and meta-analyses clearly argues that significant portion
of variance in violent/criminal behavior stems from
genetic predisposition [85, 86]. Therefore, it is essential to
incorporate this topic into contemporary criminalistics,
in an attempt to develop treatment and intervention
plans, as well as preventional support, aimed at decreasing
likelihood of exhibiting violent behavior and reducing
the extent of violence.
Acknowledgment. During this work, S.T. was
supported by the Serbian Ministry of Education, Science
and Technological Development Project No. TR34019
and the EU Commission project AREA, contract No.
316004.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
Raine A. From genes to brain to antisocial behavior. Current directions in psychological science. 2008;17(5):323-8.
Geen RG. Human Aggression. Donnerstein ED, editor. Milton Keynes: Open University Press; 1990.
Rushton JP, Fulker DW, Neale MC, Nias DK, Eysenck HJ. Altruism and aggression: the heritability of individual differences. Journal of
personality and social psychology. 1986;50(6):1192-8.
Jacobs PA, Brunton M, Melville MM, Brittain RP, McClemont WF. Aggressive behavior, mental sub-normality and the XYY male. Nature.
1965;208(5017):1351-2.
Jacobs PA, Matsuura JS, Mayer M, Newlands IM. A cytogenetic survey of an institution for the mentally retarded: I. Chromosome
abnormalities. Clinical genetics. 1978;13(1):37-60.
Brown WM. Males with an XYY sex chromosome complement. Journal of medical genetics. 1968;5(4):341-59.
Casey MD, Segall LJ, Street DR, Blank CE. Sex chromosome abnormalities in two state hospitals for patients requiring special security.
Nature. 1966;209(5023):641-2.
Jacobs PA, Price WH, Court Brown WM, Brittain RP, Whatmore PB. Chromosome studies on men in a Maximum Security Hospital.
Annals of human genetics. 1968;31(4):339-58.
Gotz MJ, Johnstone EC, Ratcliffe SG. Criminality and antisocial behaviour in unselected men with sex chromosome abnormalities.
Psychological medicine. 1999;29(4):953-62.
Nielsen J, Wohlert M. Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in
Arhus, Denmark. Birth defects original article series. 1990;26(4):209-23.
Walzer S, Bashir AS, Silbert AR. Cognitive and behavioral factors in the learning disabilities of 47,XXY and 47,XYY boys. Birth defects
original article series. 1990;26(4):45-58.
Casey MD, Blank CE, McLean TM, Kohn P, Street DR, McDougall JM, et al. Male patients with chromosome abnormality in two State
hospitals. Journal of mental deficiency research. 1972;16(3):215-56.
Stochholm K, Bojesen A, Jensen AS, Juul S, Gravholt CH. Criminality in men with Klinefelter's syndrome and XYY syndrome: a cohort
study. BMJ open. 2012;2(1):e000650.
Visootsak J, Graham JM, Jr. Social function in multiple X and Y chromosome disorders: XXY, XYY, XXYY, XXXY. Developmental
disabilities research reviews. 2009;15(4):328-32.
Miller ME, Sulkes S. Fire-setting behavior in individuals with Klinefelter syndrome. Pediatrics. 1988;82(1):115-7.
Cools R, Nakamura K, Daw ND. Serotonin and dopamine: unifying affective, activational, and decision functions. Neuropsychopharmacology:
official publication of the American College of Neuropsychopharmacology. 2011;36(1):98-113.
Davidson RJ, Putnam KM, Larson CL. Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence. Science.
2000;289(5479):591-4.
Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA. Abnormal behavior associated with a point mutation in the structural
gene for monoamine oxidase A. Science. 1993;262(5133):578-80.
Bortolato M, Shih JC. Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. International review of
199
Teodorović S. and Uzelac B.
Genetic basis of aggression: Overview and implications for legal proceedings
neurobiology. 2011;100:13-42.
20. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, et al. Aggressive behavior and altered amounts of brain serotonin and norepinephrine
in mice lacking MAOA. Science. 1995;268(5218):1763-6.
21. Huang YY, Cate SP, Battistuzzi C, Oquendo MA, Brent D, Mann JJ. An association between a functional polymorphism in the monoamine
oxidase a gene promoter, impulsive traits and early abuse experiences. Neuropsychopharmacology : official publication of the American
College of Neuropsychopharmacology. 2004;29(8):1498-505.
22. Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Human genetics. 1998;103(3):273-9.
23. Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, et al. Excess of high activity monoamine oxidase A gene promoter
alleles in female patients with panic disorder. Human molecular genetics. 1999;8(4):621-4.
24. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF. A regulatory polymorphism of the monoamine oxidase-A gene may be associated
with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry research. 2000;95(1):9-23.
25. Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, et al. MAOA, maltreatment, and gene-environment interaction
predicting children's mental health: new evidence and a meta-analysis. Molecular psychiatry. 2006;11(10):903-13.
26. Contini V, Marques FZ, Garcia CE, Hutz MH, Bau CH. MAOA-uVNTR polymorphism in a Brazilian sample: further support for the
association with impulsive behaviors and alcohol dependence. American journal of medical genetics Part B, Neuropsychiatric genetics :
the official publication of the International Society of Psychiatric Genetics. 2006;141B(3):305-8.
27. Beaver KM, DeLisi M, Vaughn MG, Barnes JC. Monoamine oxidase A genotype is associated with gang membership and weapon use.
Comprehensive psychiatry. 2010;51(2):130-4.
28. Stetler DA, Davis C, Leavitt K, Schriger I, Benson K, Bhakta S, et al. Association of low-activity MAOA allelic variants with violent crime
in incarcerated offenders. Journal of psychiatric research. 2014;58:69-75.
29. Guo G, Ou XM, Roettger M, Shih JC. The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood:
associations and MAOA promoter activity. European journal of human genetics : EJHG. 2008;16(5):626-34.
30. Beaver KM, Wright JP, Boutwell BB, Barnes JC, DeLisi M, Vaughn MG. Exploring the association between the 2-repeat allele of the MAOA
gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior. Personality and
individual differences. 2013;54(2):164-8.
31. Beaver KM, Barnes JC, Boutwell BB. The 2-repeat allele of the MAOA gene confers an increased risk for shooting and stabbing behaviors.
The Psychiatric quarterly. 2014;85(3):257-65.
32. Ficks CA, Waldman ID. Candidate genes for aggression and antisocial behavior: a meta-analysis of association studies of the 5HTTLPR
and MAOA-uVNTR. Behavior genetics. 2014;44(5):427-44.
33. Black GC, Chen ZY, Craig IW, Powell JF. Dinucleotide repeat polymorphism at the MAOA locus. Nucleic acids research. 1991;19(3):689.
34. Vanyukov MM, Moss HB, Yu LM, Deka R. A dinucleotide repeat polymorphism at the gene for monoamine oxidase A and measures of
aggressiveness. Psychiatry research. 1995;59(1-2):35-41.
35. Fowler JS, Alia-Klein N, Kriplani A, Logan J, Williams B, Zhu W, et al. Evidence that brain MAO A activity does not correspond to MAO
A genotype in healthy male subjects. Biological psychiatry. 2007;62(4):355-8.
36. Widom CS, Brzustowicz LM. MAOA and the "cycle of violence:" childhood abuse and neglect, MAOA genotype, and risk for violent and
antisocial behavior. Biological psychiatry. 2006;60(7):684-9.
37. Aslund C, Nordquist N, Comasco E, Leppert J, Oreland L, Nilsson KW. Maltreatment, MAOA, and delinquency: sex differences in geneenvironment interaction in a large population-based cohort of adolescents. Behavior genetics. 2011;41(2):262-72.
38. Moosajee M. Violence--a noxious cocktail of genes and the environment. Journal of the Royal Society of Medicine. 2003;96(5):211-4.
39. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. Role of genotype in the cycle of violence in maltreated children. Science.
2002;297(5582):851-4.
40. Beaver KM, Nedelec JL, Wilde M, Lippoff C, Jackson D. Examining the association between MAOA genotype and incarceration, anger and
hostility: The moderating influences of risk and protective factors. Journal of research in personality. 2011;45(3):279-84.
41. Fergusson DM, Boden JM, Horwood LJ, Miller AL, Kennedy MA. MAOA, abuse exposure and antisocial behaviour: 30-year longitudinal
study. The British journal of psychiatry : the journal of mental science. 2011;198(6):457-63.
42. Oreland L, Comasco E, Hallman J, Aslund C, Nilsson K. 1022–Epistatic effects of BDNF, 5HTTLPR and MAOA in interaction with
environmental adversityon adolescent criminality. 21th European Congress of Psychiatry2013.
43. Pickles A, Hill J, Breen G, Quinn J, Abbott K, Jones H, et al. Evidence for interplay between genes and parenting on infant temperament in
the first year of life: monoamine oxidase A polymorphism moderates effects of maternal sensitivity on infant anger proneness. Journal of
child psychology and psychiatry, and allied disciplines. 2013;54(12):1308-17.
44. Williams LM, Gatt JM, Kuan SA, Dobson-Stone C, Palmer DM, Paul RH, et al. A polymorphism of the MAOA gene is associated with
emotional brain markers and personality traits on an antisocial index. Neuropsychopharmacology : official publication of the American
College of Neuropsychopharmacology. 2009;34(7):1797-809.
45. Haberstick BC, Lessem JM, Hewitt JK, Smolen A, Hopfer CJ, Halpern CT, et al. MAOA genotype, childhood maltreatment, and their
interaction in the etiology of adult antisocial behaviors. Biological psychiatry. 2014;75(1):25-30.
46. Buckholtz JW, Meyer-Lindenberg A. MAOA and the neurogenetic architecture of human aggression. Trends in neurosciences.
2008;31(3):120-9.
47. McDermott R, Tingley D, Cowden J, Frazzetto G, Johnson DD. Monoamine oxidase A gene (MAOA) predicts behavioral aggression
following provocation. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(7):2118-23.
48. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, et al. Allelic variation of human serotonin transporter gene expression. Journal
of neurochemistry. 1996;66(6):2621-4.
49. Cadoret RJ, Langbehn D, Caspers K, Troughton EP, Yucuis R, Sandhu HK, et al. Associations of the serotonin transporter promoter
polymorphism with aggressivity, attention deficit, and conduct disorder in an adoptee population. Comprehensive psychiatry. 2003;44(2):88101.
50. Hranilovic D, Stefulj J, Schwab S, Borrmann-Hassenbach M, Albus M, Jernej B, et al. Serotonin transporter promoter and intron 2
polymorphisms: relationship between allelic variants and gene expression. Biological psychiatry. 2004;55(11):1090-4.
200
Romanian Journal of Legal Medicine Vol. XXIII, No 3(2015)
51. Beitchman JH, Baldassarra L, Mik H, De Luca V, King N, Bender D, et al. Serotonin transporter polymorphisms and persistent, pervasive
childhood aggression. The American journal of psychiatry. 2006;163(6):1103-5.
52. Retz W, Retz-Junginger P, Supprian T, Thome J, Rosler M. Association of serotonin transporter promoter gene polymorphism with violence:
relation with personality disorders, impulsivity, and childhood ADHD psychopathology. Behavioral sciences & the law. 2004;22(3):415-25.
53. Liao DL, Hong CJ, Shih HL, Tsai SJ. Possible association between serotonin transporter promoter region polymorphism and extremely
violent crime in Chinese males. Neuropsychobiology. 2004;50(4):284-7.
54. Conway CC, Keenan-Miller D, Hammen C, Lind PA, Najman JM, Brennan PA. Coaction of stress and serotonin transporter genotype in
predicting aggression at the transition to adulthood. J Clin Child Adolesc Psychol. 2012;41(1):53-63.
55. Lyons-Ruth K, Holmes BM, Sasvari-Szekely M, Ronai Z, Nemoda Z, Pauls D. Serotonin transporter polymorphism and borderline or
antisocial traits among low-income young adults. Psychiatric genetics. 2007;17(6):339-43.
56. Cicchetti D, Rogosch FA, Thibodeau EL. The effects of child maltreatment on early signs of antisocial behavior: genetic moderation by
tryptophan hydroxylase, serotonin transporter, and monoamine oxidase A genes. Development and psychopathology. 2012;24(3):907-28.
57. Ni X, Chan K, Bulgin N, Sicard T, Bismil R, McMain S, et al. Association between serotonin transporter gene and borderline personality
disorder. Journal of psychiatric research. 2006;40(5):448-53.
58. Fiskerstrand CE, Lovejoy EA, Quinn JP. An intronic polymorphic domain often associated with susceptibility to affective disorders has
allele dependent differential enhancer activity in embryonic stem cells. FEBS letters. 1999;458(2):171-4.
59. Lopez de Lara C, Dumais A, Rouleau G, Lesage A, Dumont M, Chawky N, et al. STin2 variant and family history of suicide as significant
predictors of suicide completion in major depression. Biological psychiatry. 2006;59(2):114-20.
60. Rujescu D, Giegling I, Bondy B, Gietl A, Zill P, Moller HJ. Association of anger-related traits with SNPs in the TPH gene. Molecular
psychiatry. 2002;7(9):1023-9.
61. Gonzalez-Castro TB, Juarez-Rojop I, Lopez-Narvaez ML, Tovilla-Zarate CA. Association of TPH-1 and TPH-2 gene polymorphisms with
suicidal behavior: a systematic review and meta-analysis. BMC psychiatry. 2014;14:196.
62. Kunugi H, Ishida S, Kato T, Sakai T, Tatsumi M, Hirose T, et al. No evidence for an association of polymorphisms of the tryptophan hydroxylase
gene with affective disorders or attempted suicide among Japanese patients. The American journal of psychiatry. 1999;156(5):774-6.
63. Ni X, Chan D, Chan K, McMain S, Kennedy JL. Serotonin genes and gene-gene interactions in borderline personality disorder in a matched
case-control study. Progress in neuro-psychopharmacology & biological psychiatry. 2009;33(1):128-33.
64. Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J, et al. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt,
major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Archives of general psychiatry. 2005;62(10):110918.
65. Oades RD, Lasky-Su J, Christiansen H, Faraone SV, Sonuga-Barke EJ, Banaschewski T, et al. The influence of serotonin- and other genes
on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings
from a family-based association test (FBAT) analysis. Behavioral and brain functions : BBF. 2008;4:48.
66. Perez-Rodriguez MM, Weinstein S, New AS, Bevilacqua L, Yuan Q, Zhou Z, et al. Tryptophan-hydroxylase 2 haplotype association with
borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls. Journal of psychiatric
research. 2010;44(15):1075-81.
67. Zill P, Baghai TC, Zwanzger P, Schule C, Eser D, Rupprecht R, et al. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform
(TPH2) gene provide evidence for association with major depression. Molecular psychiatry. 2004;9(11):1030-6.
68. De Luca V, Mueller DJ, Tharmalingam S, King N, Kennedy JL. Analysis of the novel TPH2 gene in bipolar disorder and suicidality.
Molecular psychiatry. 2004;9(10):896-7.
69. Giegling I, Hartmann AM, Moller HJ, Rujescu D. Anger- and aggression-related traits are associated with polymorphisms in the 5-HT-2A
gene. Journal of affective disorders. 2006;96(1-2):75-81.
70. Mannisto PT, Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of
the new selective COMT inhibitors. Pharmacological reviews. 1999;51(4):593-628.
71. Rujescu D, Giegling I, Gietl A, Hartmann AM, Moller HJ. A functional single nucleotide polymorphism (V158M) in the COMT gene is
associated with aggressive personality traits. Biological psychiatry. 2003;54(1):34-9.
72. Beaver KM, Wright JP, DeLisi M, Walsh A, Vaughn MG, Boisvert D, et al. A gene x gene interaction between DRD2 and DRD4 is associated
with conduct disorder and antisocial behavior in males. Behavioral and brain functions : BBF. 2007;3:30.
73. Chen TJ, Blum K, Mathews D, Fisher L, Schnautz N, Braverman ER, et al. Are dopaminergic genes involved in a predisposition to
pathological aggression? Hypothesizing the importance of "super normal controls" in psychiatricgenetic research of complex behavioral
disorders. Medical hypotheses. 2005;65(4):703-7.
74. Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Blake H, et al. Multivariate analysis of associations of 42 genes in
ADHD, ODD and conduct disorder. Clinical genetics. 2000;58(1):31-40.
75. Guo G, Roettger ME, Shih JC. Contributions of the DAT1 and DRD2 genes to serious and violent delinquency among adolescents and
young adults. Human genetics. 2007;121(1):125-36.
76. Lee HJ, Lee HS, Kim YK, Kim L, Lee MS, Jung IK, et al. D2 and D4 dopamine receptor gene polymorphisms and personality traits
in a young Korean population. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the
International Society of Psychiatric Genetics. 2003;121B(1):44-9.
77. Vaske J, Wright JP, Beaver KM. A dopamine gene (DRD2) distinguishes between offenders who have and have not been violently victimized.
International journal of offender therapy and comparative criminology. 2011;55(2):251-67.
78. Boutwell BB, Beaver KM. A biosocial explanation of delinquency abstention. Criminal behaviour and mental health : CBMH. 2008;18(1):5974.
79. Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, et al. Behavioural abnormalities in male mice lacking neuronal
nitric oxide synthase. Nature. 1995;378(6555):383-6.
80. Trainor BC, Workman JL, Jessen R, Nelson RJ. Impaired nitric oxide synthase signaling dissociates social investigation and aggression.
Behavioral neuroscience. 2007;121(2):362-9.
81. Vassos E, Collier DA, Fazel S. Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression.
201
Teodorović S. and Uzelac B.
Genetic basis of aggression: Overview and implications for legal proceedings
Molecular psychiatry. 2014;19(4):471-7.
82. Boutwell BB, Menard S, Barnes JC, Beaver KM, Armstrong TA, Boisvert D. The role of gene-gene interaction in the prediction of criminal
behavior. Comprehensive psychiatry. 2014;55(3):483-8.
83. Eisenberg DT, Mackillop J, Modi M, Beauchemin J, Dang D, Lisman SA, et al. Examining impulsivity as an endophenotype using a
behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study. Behavioral and brain functions : BBF. 2007;3:2.
84. Dick DM, Aliev F, Krueger RF, Edwards A, Agrawal A, Lynskey M, et al. Genome-wide association study of conduct disorder symptomatology.
Molecular psychiatry. 2011;16(8):800-8.
85. Tielbeek JJ, Medland SE, Benyamin B, Byrne EM, Heath AC, Madden PA, et al. Unraveling the genetic etiology of adult antisocial behavior:
a genome-wide association study. PloS one. 2012;7(10):e45086.
86. Derringer J, Corley RP, Haberstick BC, Young SE, Demmitt BA, Howrigan DP, et al. Genome-Wide Association Study of Behavioral
Disinhibition in a Selected Adolescent Sample. Behavior genetics. 2015;45(4):375-81.
87. Denno DW. Courts’ increasing consideration of behavioral genetics evidence in criminal cases: results of a longitudinal study. Mich St L
Rev. 2011;967:967-1047.
88. People v. Tanner. Court of Appeals of California, Second District, Division Three; 1970.
89. Price WH, Whatmore PB. Behaviour disorders and pattern of crime among XYY males identified at a maximum security hospital. British
medical journal. 1967;1(5539):533-6.
90. Mobley v. State. Supreme Court of Georgia; 1995.
91. State of Tennessee v. Davis Bradley Waldroup, JR.: Court of Criminal Appeals of Tennessee; 2011.
92. Baum ML. The monoamine oxidase A (MAOA) genetic predisposition to impulsive violence: Is it relevant to criminal trials? Neuroethics.
2013;6(2):287-306.
93. Baum ML, Savulescu J. Behavioral Biomarkers: What Are They Good For? Bioprediction, Biomarkers, and Bad Behavior. New York:
Oxford University Press; 2013.
202